title: Combinatory responses of proinflamamtory cytokines on nitric oxide-mediated function in mouse calvarial osteoblasts.
abstract: Combinatory responses of proinflamamtory cytokines have been examined on the nitric oxide-mediated function in cultured mouse calvarial osteoblasts. Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) induced iNOS gene expression and NO production, although these actions were inhibited by L-NG-monomethylarginine (L-NMMA) and decreased alkaline phosphatase (ALPase) activity. Furthermore, NO donors, sodium nitroprusside (SNP) and NONOate dose-dependently elevated ALPase activity. In contrast, transforming-growth factor-beta (TGF-beta) decreased NO production stimulated by IL-1beta, TNF-alpha and interferon-gamma (IFN-gamma). iNOS was expressed by mouse calvarial osteoblast cells after stimulation with IL-1beta, TNF-alpha, and IFN-gamma. Incubation of mouse calvarial osteoblast cells with the cytokines inhibited growth and ALPase activity. However, TGF-beta-treatment abolished these effects of IL-1beta, TNF-alpha and IFN-gamma on growth inhibition and stimulation of ALPase in mouse calvarial osteoblast cells. In contrast, IL-1beta, TNF-alpha, and IFN-gamma exerted growth-inhibiting effects on mouse calvarial osteoblast cells which were partly NO-dependent. The results suggest that NO may act predominantly as a modulator of cytokine-induced effects on mouse calvarial osteoblast cells and TGF-beta is a negative regulator of the NO production stimulated by IL-1beta, TNF-alpha and IFN-gamma.
authors.affiliation: Department of Orthodondritics, Kyung-Hee University College of Dental Medicine, Dongdaemun-Gu, Seoul 130-701, Republic of Korea. ygpark@khu.ac.kr
authors.forename: Young-Guk
authors.initials: YG
authors.lastname: Park
authors.forename: Kyung-Woon
authors.initials: KW
authors.lastname: Kim
authors.forename: Kwon-Ho
authors.initials: KH
authors.lastname: Song
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Lee
authors.forename: Jeong-Jin
authors.initials: JJ
authors.lastname: Hong
authors.forename: Sungk-Kwon
authors.initials: SK
authors.lastname: Moon
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D017931:DNA Primers; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D017931:DNA Primers; D053583:Interleukin-1beta; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D009599:Nitroprusside; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000469:Alkaline Phosphatase